The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils.
2018
Stammnitz, Maximilian R | Coorens, Tim HH | Gori, Kevin C | Hayes, Dane | Fu, Beiyuan | Wang, Jinhong | Martin-Herranz, Daniel E | Alexandrov, Ludmil B | Baez-Ortega, Adrian | Barthorpe, Syd | Beck, Alexandra | Giordano, Francesca | Knowles, Graeme W | Kwon, Young Mi | Hall, George | Price, Stacey | Pye, Ruth J | Tubio, Jose MC | Siddle, Hannah VT | Sohal, Sukhwinder Singh | Woods, Gregory M | McDermott, Ultan | Yang, Fengtang | Garnett, Mathew J | Ning, Zemin | Murchison, Elizabeth P
Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The two cancers have similar patterns of mutation and show no evidence of exposure to exogenous mutagens or viruses. Genes encoding PDGF receptors have copy number gains and are present on extrachromosomal double minutes. Drug screening indicates causative roles for receptor tyrosine kinases and sensitivity to inhibitors of DNA repair. Y chromosome loss from a male clone infecting a female host suggests immunoediting. These results imply that Tasmanian devils may have inherent susceptibility to transmissible cancers and present a suite of therapeutic compounds for use in conservation.
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